PMID- 14521731
OWN - NLM
STAT- MEDLINE
DCOM- 20041229
LR  - 20061115
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 83
IP  - 17
DP  - 2003 Sep 10
TI  - [The inhibitory effect of hyporesponsive peptide on human leukocyte 
      antigen-DRbeta1 specific T cell activation].
PG  - 1505-9
AB  - OBJECTIVE: To evaluate the inhibitory effect of human leukocyte antigen 
      (HLA)-DRbeta1 specific collagen II (CII) peptides with substitutions of TCR 
      binding residues on T cell activation, and explore a new therapeutic strategy for 
      T cell mediated autoimmune diseases by interfering with antigen recognition of T 
      Cell receptor (TCR). METHODS: Non-TCR binding peptides were designed by computer 
      modeling based on interaction of HLA DR1. The modified CII263-272. Intracellular 
      transfer of the modified CII peptide and its binding to HLA DR1 were studied 
      using confocal microscopy and fluorescence-activated cell sorter (FACS). The 
      effects of altered peptides on T cell activation were evaluated using an antigen 
      presenting system consisting of HLA-DR1 transgenic APC and CII specific T cells. 
      RESULTS: Computer modeling showed the side chains of 263 (F), 266 (E) fit in the 
      peptide binding groove, and form hydrogen bond with alpha1, beta1 chain of 
      HLA-DR1. The side chains of TCR specific 267 (Q) and 270 (K) protruded out of the 
      groove, which might be TCR recognizing residues. The modified CII peptides with 
      intact HLA-DR1 binding residues were bound to intracellular HLA-DR1 and expressed 
      on cell surface. The modified peptides with single residue substitution of 
      267-270 and consecutive substitution of 268-270 showed a hyporesponsive T cell 
      activation. Altered peptides 270A, sub268-270 could significantly suppress the T 
      cell activation induced by CII263-272. CONCLUSION: The altered peptides with 
      substitution of TCR binding residues are hyporesponsive in T cell activation, and 
      may competitively inhibit the T cell activation in T cell mediated autoimmune 
      diseases.
FAU - Zhou, Qiang
AU  - Zhou Q
AD  - Department of Rheumatology and Immunology, People's Hospital, Center of Health 
      Sciences, Peking University, Beijing 100044, China.
FAU - Cheng, Yong-Jing
AU  - Cheng YJ
FAU - Li, Zhan-Guo
AU  - Li ZG
FAU - Zhou, Wei-Hong
AU  - Zhou WH
FAU - Lu, Hou-Shan
AU  - Lu HS
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Collagen Type II)
RN  - 0 (HLA-DR1 Antigen)
RN  - 0 (HLA-DR4 Antigen)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Amino Acid Substitution
MH  - Collagen Type II/chemistry/genetics/immunology
MH  - Computer Simulation
MH  - HLA-DR1 Antigen/chemistry/*genetics/immunology
MH  - HLA-DR4 Antigen/chemistry/*genetics/immunology
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Lymphocyte Activation/*drug effects
MH  - Peptides/genetics/metabolism/*pharmacology
MH  - Protein Structure, Tertiary
MH  - Receptors, Antigen, T-Cell/genetics
MH  - T-Lymphocytes/drug effects/*immunology
EDAT- 2003/10/03 05:00
MHDA- 2004/12/30 09:00
CRDT- 2003/10/03 05:00
PHST- 2003/10/03 05:00 [pubmed]
PHST- 2004/12/30 09:00 [medline]
PHST- 2003/10/03 05:00 [entrez]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2003 Sep 10;83(17):1505-9.